Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily. Many BMPs are produced in bone and modulate osteogenic activity, which suggests that these proteins are involved in building bone mass. Members of the BMP family include BMP-2 and BMP-3. BMP-2 has been implicated in multiple functions associated with bone formation and growth. For example, the protein induces differentiation of osteoprogenitor cells into osteoblasts, and to enhance healing of bone fractures.
BMP-3 is also termed BMP-3A. A closely related protein termed BMP-3B is also known as growth and differentiation factor 10 (GDF-10). These two proteins show great amino acid sequence similarity in the region corresponding to the mature (fully processed) form, corresponding the C-terminal portion of the unprocessed protein. The differences between the sequences of BMP-3A and BMP-3B are located mainly outside the mature peptide regions, with the propeptides showing significant sequence divergence. BMP-3A was originally purified from bone as osteogenin and is particularly abundant in demineralized bone. Recombinant BMP-3A showed no osteogenic activity and instead was reported to antagonize the osteogenic activity of BMP-2. Zhu et al., Chin J Biotechnol. 1999; 15(3): 153-8. This result was supported by an observed increase in bone density and volume in a BMP-3A −/− knock-out mouse. Daluiski et al., Nat Genet. 2001 January;27(1):84-8.
In view of the above findings, a need exists for a manner of regulating BMP-3A activity, particularly in individuals who are in need of increased bone mass or increased bone growth, such as individuals with osteoporosis or bone fractures.